Liver disease is said to be a disease so prevalent as to harm the nation as a whole in our country. Many patients are suffering from liver disease. In addition, about 34,000 people died of hepatocarcinoma in a year. Recently, because therapeutic intervention has advanced, a clinical outcome for treatment of hepatocarcinoma has been improved. As the number of patients with advanced cancer increases, the number of people dying of what is called liver failure caused by a decrease in liver functions due to combined hepatic cirrhosis increases. Liver transplantation is ideal for treatment of liver failure. In our country, however, it is difficult to obtain sufficient number of donors. Accordingly, stem cells should be used for development of liver regenerative therapy.
Tissue stem cells such as bone marrow cells and umbilical cord blood cells are promising as stem cells that may differentiate into hepatocytes. Accordingly, many research institutes have been conducting R&D so as to realize regenerative medicine using hepatocyte transplantation therapy for patients with chronic liver failure and so as to develop a genuinely clinically applicable, efficient differentiation-inducing technology that can differentiate human tissue stem cells into functional hepatocytes.
For example, the laboratory of Prof. Shiota of Tottori University Faculty of Medicine has reported differentiation into hepatocytes by inhibiting a Wnt/β-catenin signaling pathway by using RNA interference during differentiation induction from human mesenchymal stem cells into hepatocytes (Non Patent Literatures 1 and 3 to 5). In addition, other research institutes have also been researching the differentiation induction into hepatocytes (Non Patent Literature 2 and Patent Literatures 1 and 2).
Meanwhile, a large compound library containing 4,000 or more compounds has been recently screened. Then, five low-molecular-weight compounds capable of inhibiting a Wnt/β-catenin signaling pathway have been identified (Non Patent Literatures 6 to 9).